Fulvestrant plus goserelin versus anastrozole plus goserelin versus goserelin alone for hormone receptor-positive, HER2-negative tamoxifen-pretreated premenopausal women with recurrent or metastatic breast cancer (KCSG BR10-04): a multicentre, open-label, three-arm, randomised phase II trial (FLAG study)

Eur J Cancer. 2018 Nov:103:127-136. doi: 10.1016/j.ejca.2018.08.004. Epub 2018 Sep 14.

Abstract

Background: We investigated the efficacy and safety of fulvestrant plus goserelin (F + G) versus anastrozole plus goserelin (A + G) in comparison with goserelin (G) alone in premenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), tamoxifen-pretreated metastatic breast cancer (MBC).

Patients and methods: In this multicentre, open-label, randomised phase II study, premenopausal women aged ≥18 years with HR+, HER2-, tamoxifen-pretreated MBC were randomly assigned (1:1:1) to F + G, A + G or G alone. The primary end-point was time to progression (TTP). Secondary end-points included overall survival, overall response rate, clinical benefit rate and toxicity.

Results: Of 138 eligible patients, 44 were randomly assigned to receive F + G, 47 to A + G and 47 to G alone. The median follow-up duration was 32.2 months (interquartile range: 23.69-40.86) and the median age was 43.0 years (range 23.0-55.0). The median TTP was 16.3 months (95% confidence interval [CI] 7.5-25.1) for F + G, 14.5 months (95% CI 11.0-18.0) for A + G and 13.5 months (95% CI 10.3-16.8) for G alone. Compared with G alone, the hazard ratios were 0.608 for F + G (95% CI, 0.370-0.998; p = 0.049) and 0.982 for A + G (95% CI, 0.624-1.546; p = 0.937). In terms of visceral metastasis, a stratification factor, there were no TTP differences according to treatment arm. Grade III or IV toxicities were rarely observed. Of the common adverse events, grade I arthralgia and joint stiffness were more frequently observed in the F + G than in the A + G or G-alone groups (p < 0.05, respectively).

Conclusions: F + G provides a promising new option for the treatment of premenopausal women with HR+, HER2-, tamoxifen-pretreated MBC.

Trial registration: ClinicalTrials.gov number NCT01266213 and Korean Cancer Study Group (KCSG) Breast cancer protocol number BR10-04.

Keywords: Endocrine therapy; Fulvestrant; Metastatic breast cancer; Premenopausal.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anastrozole / pharmacology
  • Anastrozole / therapeutic use*
  • Antineoplastic Agents, Hormonal / pharmacology
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Female
  • Fulvestrant / pharmacology
  • Fulvestrant / therapeutic use*
  • Goserelin / pharmacology
  • Goserelin / therapeutic use*
  • Humans
  • Neoplasm Metastasis
  • Premenopause
  • Tamoxifen / pharmacology
  • Tamoxifen / therapeutic use*

Substances

  • Antineoplastic Agents, Hormonal
  • Tamoxifen
  • Goserelin
  • Fulvestrant
  • Anastrozole

Associated data

  • ClinicalTrials.gov/NCT01266213